Bottom Line:
One patient did not tolerate the 2,400 mg dose and continued with the 1,200 mg dose.During the study period, none of the patients experienced painful crises or other significant SCD or NAC related complications.These data indicate that N-acetylcysteine treatment of sickle cell patients may reduce SCD related oxidative stress.

ABSTRACTOxidative stress is of importance in the pathophysiology of sickle cell disease (SCD). In this open label randomized pilot study the effects of oral N-acetylcysteine (NAC) on phosphatidylserine (PS) expression as marker of cellular oxidative damage (primary end point), and markers of hemolysis, coagulation and endothelial activation and NAC tolerability (secondary end points) were studied. Eleven consecutive patients (ten homozygous [HbSS] sickle cell patients, one HbSβ(0)-thalassemia patient) were randomly assigned to treatment with either 1,200 or 2,400 mg NAC daily during 6 weeks. The data indicate an increment in whole blood glutathione levels and a decrease in erythrocyte outer membrane phosphatidylserine exposure, plasma levels of advanced glycation end-products (AGEs) and cell-free hemoglobin after 6 weeks of NAC treatment in both dose groups. One patient did not tolerate the 2,400 mg dose and continued with the 1,200 mg dose. During the study period, none of the patients experienced painful crises or other significant SCD or NAC related complications. These data indicate that N-acetylcysteine treatment of sickle cell patients may reduce SCD related oxidative stress.

Mentions:
Eleven patients (10 HbSS and 1 HbS-β0-thalassemia; median age 23 years (range 20–47), 6 male, 5 female) who met eligibility criteria, were included in the study. One patient (P4) discontinued using NAC after 3 weeks and withdrew from the study. Two patients who used <80% of prescribed dosing are shown in gray in the figures. One patient on the 2,400 mg NAC dose had gastro-intestinal complaints that disappeared after switching to 1,200 mg on the second day of treatment which she continued using (P6). No other patient reported adverse events. Levels of hemoglobin, LDH, and bilirubin and reticulocyte and leukocyte counts did not change significantly (Fig. 1). Sickle cell patients had significantly lower whole blood total glutathione and GSH levels as compared to healthy controls (Fig. 2a). Total glutathione levels increased during treatment period in patients of both 1,200 mg (from 136 (100–198) to 169 (121–221) μmol/l) and 2,400 mg (from 150 (136–165) to 163 (142–178) μmol/l) dose groups (Fig. 3, panels a and b), with the differences being statistically significant when analyzing the two dose groups combined (from 150 (113–168) to 167 (142–179) μmol/l, P < 0.05).Fig. 1

Mentions:
Eleven patients (10 HbSS and 1 HbS-β0-thalassemia; median age 23 years (range 20–47), 6 male, 5 female) who met eligibility criteria, were included in the study. One patient (P4) discontinued using NAC after 3 weeks and withdrew from the study. Two patients who used <80% of prescribed dosing are shown in gray in the figures. One patient on the 2,400 mg NAC dose had gastro-intestinal complaints that disappeared after switching to 1,200 mg on the second day of treatment which she continued using (P6). No other patient reported adverse events. Levels of hemoglobin, LDH, and bilirubin and reticulocyte and leukocyte counts did not change significantly (Fig. 1). Sickle cell patients had significantly lower whole blood total glutathione and GSH levels as compared to healthy controls (Fig. 2a). Total glutathione levels increased during treatment period in patients of both 1,200 mg (from 136 (100–198) to 169 (121–221) μmol/l) and 2,400 mg (from 150 (136–165) to 163 (142–178) μmol/l) dose groups (Fig. 3, panels a and b), with the differences being statistically significant when analyzing the two dose groups combined (from 150 (113–168) to 167 (142–179) μmol/l, P < 0.05).Fig. 1

Bottom Line:
One patient did not tolerate the 2,400 mg dose and continued with the 1,200 mg dose.During the study period, none of the patients experienced painful crises or other significant SCD or NAC related complications.These data indicate that N-acetylcysteine treatment of sickle cell patients may reduce SCD related oxidative stress.

ABSTRACTOxidative stress is of importance in the pathophysiology of sickle cell disease (SCD). In this open label randomized pilot study the effects of oral N-acetylcysteine (NAC) on phosphatidylserine (PS) expression as marker of cellular oxidative damage (primary end point), and markers of hemolysis, coagulation and endothelial activation and NAC tolerability (secondary end points) were studied. Eleven consecutive patients (ten homozygous [HbSS] sickle cell patients, one HbSβ(0)-thalassemia patient) were randomly assigned to treatment with either 1,200 or 2,400 mg NAC daily during 6 weeks. The data indicate an increment in whole blood glutathione levels and a decrease in erythrocyte outer membrane phosphatidylserine exposure, plasma levels of advanced glycation end-products (AGEs) and cell-free hemoglobin after 6 weeks of NAC treatment in both dose groups. One patient did not tolerate the 2,400 mg dose and continued with the 1,200 mg dose. During the study period, none of the patients experienced painful crises or other significant SCD or NAC related complications. These data indicate that N-acetylcysteine treatment of sickle cell patients may reduce SCD related oxidative stress.